dbSNP rs374363601: NOMO3:p.Thr350Asn (chr16-16255805-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004067.4(NOMO3):c.1049C>A(p.Thr350Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T350I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.0000014 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

NOMO3
NM_001004067.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32

Variant links:

Genes affected

NOMO3 (HGNC:25242): (NODAL modulator 3) This gene encodes a protein originally thought to be related to the collagenase gene family. This gene is one of three highly similar genes in a duplicated region on the short arm of chromosome 16. These three genes encode closely related proteins that may have the same function. The protein encoded by one of these genes has been identified as part of a protein complex that participates in the Nodal signaling pathway during vertebrate development. Mutations in ABCC6, which is located nearby, rather than mutations in this gene are associated with pseudoxanthoma elasticum. [provided by RefSeq, Jul 2008]

NOMO3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25851554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOMO3	NM_001004067.4 link	c.1049C>A	p.Thr350Asn	missense_variant	Exon 10 of 31	ENST00000399336.9	NP_001004067.1	P69849Q1LZN2
NOMO3	XM_005255318.2 link	c.1049C>A	p.Thr350Asn	missense_variant	Exon 10 of 32		XP_005255375.1	J3KN36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOMO3	ENST00000399336.9 link	c.1049C>A	p.Thr350Asn	missense_variant	Exon 10 of 31	1	NM_001004067.4	ENSP00000382274.4		P69849

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244168

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000139

AC:

AN:

1436016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000238

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.11

Sift

Benign

0.30

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.41

B;.

Vest4

0.47

MutPred

0.42

Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);

MVP

0.24

ClinPred

0.14

GERP RS

2.4

Varity_R

0.087

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over